Cosmetic compositions which are on the market today are known to improve the appearance of the skin. They are usually used to prevent or treat signs of skin ageing expressed as loss of firmness, decrease of skin thickness, fine lines, wrinkles, loss of elasticity, sagging, dryness, age spots, diminished rate of turnover, abnormal desquamation, decrease of the density and disorganization of the extra-cellular matrix in the dermis and other histological changes. It is well known that exposure to oxidative stress, UV rays, irritants, allergens, and various environmental toxins have an impact on these properties and accelerate skin ageing, so that cosmetic compositions are generally designated as anti-ageing compositions.
The skin consists of three layers, the epidermis, the dermis and the subcutaneous tissue (hypodermis), of which the dermis is composed of two distinct layers, the papillary and reticular dermis.
The skin's extra-cellular matrix is a complex network of macromolecules, such as collagen or elastic fibers, glycoproteins, glycosaminoglycans and proteoglycans. It provides a physical framework to assume mechanical strength and participates in cell metabolism regulation. In the dermis more than 70% of the proteins are collagens. Collagen is responsible for the skin's strength. It is produced by cells called fibroblasts, which are found scattered throughout the dermis. One major type of collagen in the human skin dermis is collagen type I, which forms the network of fibers.
The dermis also contains quantitatively minor collagens, such as collagen type XII and collagen type XIV, members of the FACIT (Fibril Associated Collagens with Interrupted Triple helices). FACITs are important for the good quality of the extra-cellular matrix. They are found associated with collagens fibers in the interfibrillar space and are involved in the correct structuring of the fiber network.
The other fibers composing the extra-cellular matrix of dermis are elastic fibers, mainly composed of tropoelastin that are polymerized on microfibrils. Elastic fibers are directly involved in the elastic property of the skin and are also produced by the fibroblasts in the skin dermis.
During skin ageing, the synthesis rate of collagen and elastin fibers decreases while their degradation level strongly increases. The result of these two ageing processes is a strong reduction of the amount of fibers in the dermis, inducing alterations of the skin properties.
The production of the extra-cellular matrix and of enzymes involved in its degradation is to a great extent controlled by fibroblasts and the balance between synthesis and degradation is fundamental for correct skin homeostasis. Some growth factors, such as transforming growth factors (TGF) or connective tissue growth factor (CTGF) are signals that strongly stimulate fibroblast growth and the production of the extra-cellular matrix.
The metabolism of the fibroblast is modified during ageing due to many factors. Alteration of the communication molecules, homeostasis or accumulation of altered proteins by reactive oxygen species (ROS) are some causes of this fibroblast metabolism modification. ROS can be produced by endogenous metabolism of cells, mainly in the mitochondria. In addition, ROS production may result from extrinsic factors such as UV exposure or pollution strongly oxidant. To fight against oxidative stress, cells have different systems to degrade endogenous or exogenous ROS, such as catalase or peroxidise. Cells also possess some defence systems to revert the ROS-induced modifications of proteins. For example, oxidized methionines can be reverted by the methionine sulfoxide reductases. These enzymes may be located in the different cell compartments. For example, glutaredoxin-2 is located either in nucleus or in mitochondria, the main localization of endogenous ROS production. Glutaredoxins and other proteins have the property to disrupt disulfide bridges induced by ROS. Nevertheless, these repair systems are also deteriorated during ageing.
Hence there is a need for effective protection of the skin against environmental influences.
Some cosmetic and dermopharmaceutical compositions containing oligopeptides are already on the market. Tripeptides such as N-palmitoyl-Gly-His-Lys (in Matrixyl® 3000 available from De Wolf Chemical, USA) palmitoyl-tripeptide-3 (SYN®-COLL by Pentapharm, Ltd. Switzerland) and tetrapeptides as N-palmitoyl-Gly-Gln-Pro-Arg (SEQ ID NO:2) (in Matrixyl® 3000 available from De Wolf Chemical, USA) are used in cosmetics due to their dermal stimulating properties. U.S. Pat. No. 6,974,799 is related to pharmaceutical, personal care and cosmetic compositions containing these oligopeptides useful for treating visible signs of ageing including wrinkles, stretch marks and dark circles.
Cosmetic or dermopharmaceutical compositions with peptides of the general sequence X-Thr-Thr-Lys-Y, wherein in particular X is lysine and Y is serine are used for healing, hydrating and improving skin appearance during natural or induced ageing (U.S. Pat. No. 6,620,419B).
Topical personal care and skin care compositions comprising an effective amount of a tetrapeptide selected from the group of tetrapeptides with the motif GX1X2G, PX1X2P, or PX1X2K; an effective amount of at least one additional active ingredient and a dermatologically acceptable carrier is object of the International application WO 2009/068351A. The peptides disclosed in WO2009/068351 act on collagen fibers present in the dermis both in quantity (COL1A1, COL1A2 gene expression and collagen production) and organization (FN1 gene expression) resulting in an increase of skin firmness and on hyaluronic acid production (HAS1 gene expression) increasing the hydration of the skin. The international application WO 2008/020954 discloses cosmetic compositions comprising dermal stimulating palmitoyl oligopeptides that regenerate the dermal matrix and a rapid acting muscle relaxant derived from the extract of the plant Acemella oleracea. By limiting cutaneous deformation caused by the contraction of facial muscles the extract increases the efficiency of the peptides in reducing expression lines.
Val-Leu-Leu-His (SEQ ID NO:3) tetrapeptide is a consensus sequence between human IL-1a and bovine parotine. It has been shown to stimulate proliferation of epithelial cells from rabbit cornea, and to exhibit a significant wound healing activity on injured rabbit cornea. (Hara et al., Exp Eye Res, 2001, 72, 107-13).
Aim of present invention was to provide a safe product for cosmetic skin treatment, in particular to improve the appearance of the skin and to improve skin elasticity resulting in body firming and to reduction of visible signs of ageing.